P990: T CELL RESPONSE AND OMICRON VARIANT NEUTRALISATION FOLLOWING VACCINATION AGAINST SARS-COV-2 IN PATIENTS WITH CHRONIC MYELOID DISORDERS
Authors: P. Harrington, J. Saunders, C. Saha, A. Sheikh, R. Dillon, K. Raj, L. Cadman-Davies, T. Lechmere, H. Khan, C. Woodley, S. Asirvatham, N. Curto-Garcia, J. O’Sullivan, S. Kordasti, D. Radia, D. McLornan, M. Malim, K. Doores, C. Harrison, H. de Lavallade
Journal: HemaSphere (2022)

Background: Concerns remain over the response to vaccination against SARS-CoV-2 in patients with haematological malignancy. Aims: Herein, we report a comprehensive immunological evaluation of the response to SARS-CoV-2 vaccination in patients with chronic myeloid neoplasms (MPN). Methods: Antibody response was assessed using anti-Spike (anti-S) IgG with anti-nucleocapsid (anti-N) IgG used to determine previous infection. Neutralising antibody analysis was performed assessing inhibitory effect of plasma on entry of HIV-1 particles expressing Wuhan and omicron variant spike proteins into cells expressing ACE-2 receptor. T cell response was assessed using flow cytometric evaluation of intracellular pro-inflammatory cytokines and surface exhaustion markers upon re-exposure to S peptides (Miltenyi) in T cell subsets. Subsequently, T cell response was evaluated using a fluorospot assay assessing IFNg/IL-2 secretion upon re-exposure to S peptides (Mabtech). Plates were analysed using the IRIS reader providing both spot-forming unit (SFU) frequency and relative spot volume (RSV). Results: Samples were collected in 102 patients with MPN or post allo-SCT. Testing was performed in 37 MPN patients after one dose, 61 after 2 doses and 30 after 3 doses to date. An anti-S IgG response was observed in 81.1% (30/37) of MPN patients after a first dose, increasing after two doses to 91.7% (55/60). Those with previous infection had higher anti-S IgG and neutralising antibody levels following two doses of vaccine (p=0.0002/p<0.0001). MPN patients receiving the BNT162b2 vaccine had higher anti-S IgG and neutralising antibody levels compared with those receiving ChAdOx-1 (p=0.05/p=0.04). The proportion of patients on ruxolitinib (rux) with a negative or borderline response after two doses was higher than observed in other patients (5/10 vs 5/47, p=0.01). Preliminary analysis in 20 patients showed reduced neutralisation of omicron compared with the Wuhan spike, with neutralising antibody ID50 of 93 vs 218 (p=0.06, Fig. 1a). Using fluorospot analysis after two doses, an overall T-cell response was observed in 88.3% (53/60) patients. Patients on rux had lower SFUs for IFN and IL-2 and amongst those on treatment, RSV of IFNg was again lowest in patients on rux, with mean RSV of 2942 vs 7990 in patients on hydroxycarbamide and 6687 in peg-IFNa (p=0.016/p=0.0008). T cells expressed increased exhaustion markers upon re-exposure to S peptides in patients with CML following vaccination. After a third dose, T cell response was assessed in 30 patients with a positive response in 90% (27/30). IFNg SFUs and RSV were significantly higher after 3 vs 2 doses at 242 and 9184 vs 72 and 5031 (p=0.0004/<0.0001, Fig. 1b,c). Patients on rux after 3 doses had lower SFU and RSV of IFNg than other patients at 79 and 7690 vs 302 and 9727 (p=0.035/0.04 Fig 1d,e). Patients on rux were more likely to have a negative T cell response than other patients (4/8 vs 20/22, p=0.0294). Patients with a diagnosis of MF had lower SFU and RSV for IFNg than patients with CML, PV and ET (SFU: 93 vs 294, 224 and 446, p=0.09/0.002/0.15, RSV: 7532 vs 9528, 10499 and 10630, p=0.08/0.001/0.01, Fig. 1f) Image:Summary/Conclusion: We show overall high frequency of seroconversion and memory T cell responses but demonstrate the need for alternative strategies in some groups, including patients taking ruxolitinib. The increase in T cell reactivity after 3 doses is of particular significance in view of the reduced neutralisation of the now dominant omicron variant, with studies showing T cell functionality is maintained against omicron. Updated results will be presented.